This project has two principal objectives. One is to understand the structural basis of acetylcholine receptor function. Such understanding should be relevant not only to neuromuscular, but also in some degree to studies of neurotransmitter receptor in the central nervous system. The second objective is to understand the pathological mechanisms involved in myasthenia gravis. These studies are intended to improve diagnosis and therapy of this disease in particular, but may also be relevant as a model for the study of other diseases involving autoimmune response to particular cell surface components. Structure of receptor purified from fish electric organs and mammalian muscle is being characterized by conventional biochemical techniques, but also with special emphasis on the use of immunochemical techniques. Immunochemical techniques are also being used to study receptor metabolism. The structural basis of receptor function is being investigated through immunological techniques and through studies of purified receptor artificially reassociated with a lipid environment. Animals immunized with purified receptor are being studied as a model of human myasthenia gravis. These studies are providing a substantial qualitative and quantitative understanding of the pathological mechanisms involved. Sera and muscle from patients with myasthenia gravis are being studied in parallel with those of animals with experimental autoimmune myasthenia gravis.